کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1373832 | 981908 | 2006 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Discovery and initial development of a novel class of antibacterials: Inhibitors of Staphylococcus aureus transcription/translation Discovery and initial development of a novel class of antibacterials: Inhibitors of Staphylococcus aureus transcription/translation](/preview/png/1373832.png)
The novel bacterial transcription/translation (TT) inhibitor 1 was identified through a combination of high throughput screening and exploratory medicinal chemistry. Initial optimization of the anthranilic acid moiety and sulfonamide amine diversity was accomplished via 1- and two-dimensional solution phase libraries, resulting in an improvement in the MIC of the lead from 64 to 8 μg/mL (compound 4l). Subsequent modification of the central aromatic ring and further refinement of the sulfonamide amines required the development of a solid phase route on Wang resin. The resulting libraries generated a number of potent antibacterials with MICs of ⩽1 μg/mL (e.g., 10b, 12, and 13). During the course of this work, it became apparent that the antibacterial activity of the series is not fully correlated with TT inhibition, suggesting that at least one additional mechanism of action is operative.
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Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 24, 15 December 2006, Pages 6173–6177